title: Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women.
abstract: OBJECTIVE
  Oral contraceptives such as norgestimate-ethinyl estradiol (Ortho Tri-Cyclen®) are commonly prescribed in the HIV-infected patient population. A placebo-controlled, randomized, two-period crossover study in healthy HIV-seronegative subjects was conducted to assess the effect of raltegravir on the pharmacokinetics of the estrogen and progestin components of norgestimate-ethinyl estradiol [ethinyl estradiol (EE) and norelgestromin (NGMN), an active metabolite of norgestimate (NGT)].
  
  
  METHODS
  In each of two periods, nineteen healthy women established on norgestimate-ethinyl estradiol contraception (21 days of active contraception; 7 days of placebo) received either 400 mg raltegravir or matching placebo twice daily on days 1-21. Pharmacokinetics were analysed on day 21 of each period.
  
  
  RESULTS
  The geometric mean ratio (GMR) and 90% confidence interval (CI) for the EE component of norgestimate-ethinyl estradiol when co-administrated with raltegravir relative to EE alone was 0.98 (0.93-1.04) for the area under the concentration-time curve from 0 to 24 h (AUC(0-24 h) ) and 1.06 (0.98-1.14) for the maximum concentration of drug in the plasma (C(max) ); the GMR (90% CI) for the NGMN component of norgestimate-ethinyl estradiol when co-administered with raltegravir relative to NGMN alone was 1.14 (1.08-1.21) for AUC(0-24 h) and 1.29 (1.23-1.37) for C(max) . There were no discontinuations due to a study drug-related adverse experience, nor any serious clinical or laboratory adverse experience.
  
  
  CONCLUSIONS
  Raltegravir has no clinically important effect on EE or NGMN pharmacokinetics. Co-administration of raltegravir and an oral contraceptive containing EE and NGT was generally well tolerated; no dose adjustment is required for oral contraceptives containing EE and NGT when co-administered with raltegravir.
authors.affiliation: Merck Research Labs, Merck & Co., Inc., Whitehouse Station, NJ 07065-0900, USA. matt_anderson@merck.com
authors.forename: Matt S
authors.initials: MS
authors.lastname: Anderson
authors.forename: William D
authors.initials: WD
authors.lastname: Hanley
authors.forename: Allison R
authors.initials: AR
authors.lastname: Moreau
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Bieberdorf
authors.forename: James T
authors.initials: JT
authors.lastname: Kost
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Wenning
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stone
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Marian
authors.initials: M
authors.lastname: Iwamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics*; D004967:Estrogens / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; C118333:HIV-1 integrase (147-175); D010446:Peptide Fragments; D011760:Pyrrolidinones; D009644:Norgestrel; D000068898:Raltegravir Potassium; D004958:Estradiol; C017576:norgestimate